Direct platelet adhesion potentiates group 2 innate lymphoid cell functions
Direct platelet adhesion potentiates group 2 innate lymphoid cell functions
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DOI：
10.1111/all.15057
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发表时间：
2021-08-24
期刊：
影响因子：
12.4
通讯作者：
Morita, Hideaki
中科院分区：
文献类型：
--
作者：
Orimo, Keisuke;Tamari, Masato;Morita, Hideaki
血小板被认为参与哮喘的病理生理，可能是通过直接粘附炎症细胞，包括2组先天淋巴样细胞（ILC2s）。在这里，我们试图阐明血小板粘附ILC2s在体外和体内的作用，以及所涉及的机制。方法采用野生型和c-mpl（-/-）小鼠，建立交替菌诱导的ilc2依赖性气道炎症模型。将纯化的CD41（+）和CD41(-)ILC2s与IL-2和IL-33一起培养，检测体外2型（T2）细胞因子的产生和细胞增殖。利用流式细胞术分选的CD41（+）和CD41(-)ILC2s的RNA-seq数据分离ilc2特异性基因。流式细胞术检测小鼠和人组织中CD41和粘附相关分子在ILC2s上的表达。结果与野生型小鼠相比，c-mpl（-/-）小鼠的T2炎症和ILC2s产生的T2细胞因子明显减少。当暴露于IL-2和IL-33时，血小板粘附的ILC2s增殖显著，T2细胞因子的产生增强。ilc2特异性基因的功能与细胞发育和功能有关。上游调控分析确定了15个分子，被认为参与ILC2的激活。CD41在人PBMCs和小鼠肺ILC2s中的表达水平高于继发性淋巴组织，但它们与p -选择素糖蛋白配体-1或CD24的表达水平无关。结论血小板自发粘附ILC2s，可能在外周血和气道中，从而增强ILC2s对IL-33的反应。
Background Platelets are thought to be involved in the pathophysiology of asthma, presumably through direct adhesion to inflammatory cells, including group 2 innate lymphoid cells (ILC2s). Here, we tried to elucidate the effects of platelet adhesion to ILC2s in vitro and in vivo, as well as the mechanisms involved. Methods Alternaria-induced ILC2-dependent airway inflammation models using wild-type and c-mpl(-/-) mice were evaluated. Both purified CD41(+) and CD41(-)ILC2s were cultured with IL-2 and IL-33 to determine in vitro Type 2 (T2) cytokine production and cell proliferation. RNA-seq data of flow-cytometry-sorted CD41(+) and CD41(-)ILC2s were used to isolate ILC2-specific genes. Flow cytometry was performed to determine the expression of CD41 and adhesion-related molecules on ILC2s in both mouse and human tissues. Results T2 inflammation and T2 cytokine production from ILC2s were significantly reduced in the c-mpl(-/-) mice compared to wild-type mice. Platelet-adherent ILC2s underwent significant proliferation and showed enhanced T2 cytokine production when exposed to IL-2 and IL-33. The functions of ILC2-specific genes were related to cell development and function. Upstream regulator analysis identified 15 molecules, that are thought to be involved in ILC2 activation. CD41 expression levels were higher in ILC2s from human PBMCs and mouse lung than in those from secondary lymphoid tissues, but they did not correlate with the P-selectin glycoprotein ligand-1 or CD24 expression level. Conclusion Platelets spontaneously adhere to ILC2s, probably in the peripheral blood and airways, thereby potentiating ILC2s to enhance their responses to IL-33.